Disposable Systems as a Platform Technology for R&D and Clinical Supply

In this month's column, we continue talking to users about their experience implementing single-use technology. This month, Detlef Eisenkrätzer of Roche talks about Roche's experience deploying single-use bioreactors for early development and clinical supply of mammalian cell-based products.

Since 2006, Eisenkrätzer has been the director of the company's non-GMP pilot plant at the Penzberg Biotech Research Center, responsible for process optimization, scale-up, and technology transfer. For this project, carried out over a two-year period, he coordinated technical requirements and user resources among all the departments involved to ensure that all departments, from research to clinical supply, established the same technologies.

Q: What were the main drivers for this in-depth analysis and comparison of single-use bioreactors?

Andrew Sinclair

Our objective was to increase the number of new products developed per year. When we calculated how much it was going to cost us to increase capacity based on stainless steel, we realized that this was going to be far too expensive. Cost was the main driver, along with uncertainty regarding the profile of processes to be implemented in terms of scale and the capacity required.

Q: What were the key problems you faced?

Lack of experience with stirred single-use bioreactors (SUBs) was the key issue. We have a long tradition of building stainless steel pilot plants, so for disposables, there was a lot of uncertainty as to how to go about things.

Q: Did you look to other companies to provide support?

Yes, we used external groups to carry out a number of studies. NNE Pharmaplan supported us with concept studies in terms of layout and infrastructure. Through the use of disposables we were able to reduce our plant footprint by 23%.

Biopharm Services provided us with process modelling and cost of goods analysis with a software package to analyze a particular installation. Here, the analysis demonstrated that significant savings could be achieved through a targeted implementation of disposables.

The lifecycle assessment of the SUBs was supported by ESU Services and demonstrated that CO2 emissions were reduced by 65%, electricity by 42%, air by 98%, and steam by 80%, whereas chilled water increased by 12% and oxygen 100%.

We also wanted to gain experience from other end users. We made visits to Genentech and Lonza. We developed our own waste management concepts.

Q: How did you develop the methodology for this analysis?

We used our global guidelines for the methodology development of when to look at new technologies. The team defines the approach to implementation. The guidelines require that key stakeholders have input; in this case, this included process R&D, manufacturing, procurement, engineering, and quality assurance (QA).

Q: What areas needed the most analysis?

Single-use sensors. We are collaborating directly with the sensor companies to work on the integration and improvement of these sensors.

Q: How successful was your methodology?

The benefit of a standardized procedure is that you get all the users around the table, and by basing discussions on data, you build a rational consensus. The evaluations gained increased credibility and acceptance as each department evaluated more than one disposable type.

Q: Did the list of bioreactors you compared comprise all the key suppliers at that time?

We evaluated the following configurations:

two SUB types with rocking motion for seed train cultivation

four stirred SUB types with sizes from 200 to 500 L

five automation systems for SUBs.

Whenever possible, automation and bag systems have been combined in different variants.

Our main focus was on vendors with a global presence and global support because these systems would be supplied to our sites in Europe, Asia, or the US.

Q: What criteria did the suppliers have to meet?

The films have to comply with USP Class VI requirements, so we pay attention to whether the suppliers make the films themselves or buy them, and what the manufacturing and quality systems are that they have in place.

An important criteria was that the vendor could supply SUBs from 50 to 1,000-L. There were not many companies who had a 1,000 L bioreactor readily available when we carried out this evaluation, so that limited our evaluation. There may be more now.